A complex of cholesterol, phospholipid and protein has been described in the adrenal which is analogous to the liver-SCP in stimulating cholesterol biosynthesis and which serves as the active substrate for the cholesterol side-chain cleavage (CSCC) enzymes of the adrenal mitochondrial P450 system. The adrenal activator which is obtained by heating an extract of mitochondrial acetone powder in a boiling water bath for 2 min., is devoid of all enzyme activity and has no active component of the P450 system. Work is in progress to identify the protein which is believed to be a specific carrier for cholesterol. Phospholipid (above 10 microns) which can be shown to stimulate liver- SCP and cholesterol biosynthesis, and which enhances cholesterol esterification, will inhibit the mitochondrial (CSCC) enzyme system. The stimulation of the CSCC enzyme system most likely is a result of a solubilizing effect of the activator on the sterol-phospholipid micelle. Four major aspects of steroidogenesis to be considered are: 1) the association of the adrenal activator to the P450 enzyme system 2) the relationship of the activator to regulation by ACTH and cyclic AMP 3) methods to block or inhibit steroidogenesis via the activator-enzyme complex 4) role of the activator in abnormal conditions such as adrenal carcinoma. Using the techniques of isolated intact adrenal cells and superfusion, the effects of stimulators to adrenal cells in terms of cyclic AMP and cyclic GMP and the relationship of these factors to the adrenal activator will be explored.